Ion channels: what they are, types. and how they function in cells.

An overview of what ion channels are and what their varieties and functions are.

Ion channels are protein complexeslocated in cell membranes, which regulate vital processes such as the heartbeat or the transmission of signals between neurons.

In this article we will explain what they are, what their function and structure are, what kinds of ion channels exist and their relationship with various diseases.

What is an ion channel?

By ion channels we mean protein complexes filled with aqueous pores, which allow the ions to pass throughThey allow ions to flow from one side of the cell membrane to the other. These channels are present in all cells, of which they are an essential component.

Each cell is surrounded by a membrane that separates it from the outside environment. Its lipid bilayer structure is not easily permeable to polar molecules such as amino acids or ions. Therefore, it is necessary to transport these substances in and out of the cell by means of membrane proteins such as pumps, transporters and ion channels.

The channels are made up of one or more distinct proteins called subunits (alpha, beta, gamma (alpha, beta, gamma, etc.). When several of them join together, they create a circular structure in the center of which there is a hole or pore, which allows the passage of ions.

One of the particularities of these channels is their selectivity; that is, they determine the passage of some inorganic ions and not others, depending on the diameter and distribution of the pore.depending on the diameter and distribution of their amino acids.

The opening and closing of ion channels is regulated by various factors; a specific stimulus or sensor determines that they fluctuate from one state to another by altering their composition.

Let us now see what functions they perform and what their structure is.

Functions and structure

Behind essential cellular processes, such as the secretion of neurotransmitters or the transmission of electrical signals, lie the ion channels, which confer electrical and excitable capacities to the cells.. And when they fail, numerous pathologies can occur (which we will discuss later).

The structure of the ion channels takes the form of transmembrane proteins and act as a system of gates to regulate the to regulate the passage of ions (potassium, sodium, calcium, chlorine, etc.) through pores.

Until a few years ago, it was thought that the pores and the voltage sensor were coupled through a linker (a coil of about 15 amino acids), which can be actuated by the movement of the voltage sensor. This coupling mechanism between the two parts of the ion channel is the canonical mechanism that has always been theorized.

Recently, however, new research has uncovered another pathway involving an amino acid segment that involves an amino acid segment consisting of part of the voltage sensor and part of the pore.. These two segments would fit together like a kind of zipper to trigger the opening or closing of the channel. In turn, this new mechanism could explain recent discoveries, in which some voltage-regulated ion channels (some in charge of functions such as Heart beating) have been detected with only a single linker.

Voltage-regulated ion channels are only one of the existing types of channels, but there are more: let's see below what they are.

• You may be interested in "What are the parts of the neuron?".

Types of ion channels

The mechanisms for the activation of ion channels can be of several types: by ligand, by voltage or by mechanosensitive stimuli.

1. Ligand-regulated ion channels

These ion channels open in response to the binding of specific molecules and neurotransmitters.. This opening mechanism is due to the interaction of a chemical substance (which can be a hormone, a peptide or a neurotransmitter) with a part of the channel called a receptor, which generates a change in free energy and modifies the conformation of the protein opening the channel.

The acetylcholine receptor (a neurotransmitter involved in the transmission of signals between motor nerves and muscles) of the nicotinic type, is one of the most studied ligand-regulated ion channels. It is composed of 5 subunits of 20 amino acids and is involved in basic functions such as voluntary control of movement, memory, attention, sleep, alertness and anxiety..

2. Voltage-regulated ion channels

This type of channel open in response to changes in the electrical potential across the plasma membrane.. Voltage-regulated ion channels are involved in the transmission of electrical impulses, generating action potentials due to changes in the difference in electrical charges on both sides of the membrane.

Ion flux takes place in two processes: activation, a voltage-dependent process: the channel opens in response to changes in membrane potential (electrical potential difference on both sides of the membrane); and inactivation, a process that regulates channel closure.

The main function of the voltage-regulated ion channels is the generation of action potentials and their propagation.. There are several types and the main ones are:

2.1. Na+ channel

These are transmembrane proteins that allow the passage of sodium ions through the cell. Ion transport is passive and depends only on the electrochemical potential of the ion (it does not require energy in the form of ATP molecule). In neurons, sodium channels are responsible for the rising phase of the action potential (depolarization). (depolarization).

2.2. K+ channel

These ion channels constitute the most heterogeneous group of membrane structural proteins. In neurons, depolarization activates K+ channels and facilitates the outflow of K+ from the nerve cell, leading to a repolarization of the membrane potential.

2.3. Ca++ channel

Calcium ions promote the fusion of the synaptic vesicle membrane (structures located at the end of the neuronal axon and responsible for secreting neurotransmitters) with the axon terminal membrane in the neuron, stimulating the release of acetylcholine into the synaptic cleft by a mechanism of exocytosis..

2.4. Cl- channel

This type of ion channels is responsible for regulating cell excitability, cell-to-cell transport, as well as PH and cell volume management. Membrane-localized channels stabilize the membrane potential in excitable cells. They are also responsible for the inter-cell transport of water and electrolytes..

3. Ion channels regulated by mechanosensitive stimuli

These ion channels open in response to mechanical actions.. They can be found, for example, in Paccini's corpuscles (skin sensory receptors that respond to rapid vibrations and deep mechanical pressure), which open by stretching the cell membrane through the application of tension and/or pressure.

Canalopathies: pathologies associated with these molecules

From a physiological point of view, ion channels are fundamental to homeostatic are essential for the homeostatic equilibrium of our organism.. Their dysfunction causes a whole series of diseases, known as channelopathies. These can be caused by two types of mechanisms: genetic alterations and autoimmune diseases.

Among the genetic alterations are mutations that occur in the coding region of the gene for an ion channel. It is common for these mutations to produce polypeptide chains that are not processed correctly and are not incorporated into the plasma membrane; or, when the subunits are coupled and the channels are formed, they are not functional.

Another frequent possibility is that, even though they are functional channels, they end up showing altered kinetics. Whatever the case, they usually lead to gain or loss of channel function.

Also mutations in the promoter region of the gene coding for an ion channel may also occur.. This can cause underexpression or overexpression of the protein, resulting in changes in the number of channels, which would also lead to an increase or decrease in their functionality.

Currently, multiple pathologies associated with ion channels are known in different tissues. At the musculoskeletal level, mutations in the voltage-gated Na+ , K+ , Ca++ and Cl- channels and in the acetylcholine channel lead to disorders such as hyper- and hypokalemic paralysis, myotonias, malignant hyperthermia and myasthenia..

At the neuronal level, it has been proposed that alterations in voltage-gated Na+ channels, voltage-gated K+ and Ca++ channels, acetylcholine-activated channel or glycine-activated channel could explain disorders such as epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton syndrome, Alzheimer's disease, Parkinson's disease and schizophrenia.

Bibliographic references:

• J. T. Menéndez, "Pores and ion channels regulate cellular activity," in Anales de la Real Academia Nacional de Farmacia, 2004, p. 23.
• Ana I. Fernández-Mariño, Tyler J. Harpole, Kevin Oelstrom, Lucie Delemotte and Baron Chanda. “Gating interaction maps reveal a noncanonical electromechanical coupling mode in the Shaker K+ channel”. Nature Structural & Molecular Biology 25: 320–326, abril de 2018.
• G. Eisenman y J.A. Dani. Annu (1987). An introduction to molecular architecture and permeability of ion channels. Rev. Biophys. Biophys. Chem, 16. pp. 205-226.
• Aidley, D. J. (1989) The physiology of excitable cells. Cambridge University Press.